Novidin

Package Leaflet: Information for the User

Novidin, 400 mg, Film-Coated Tablets

Hydroxychloroquine sulfate

Read the package leaflet carefully before taking the medicine, as it contains important information for you.

• You should keep this leaflet, as you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the Package Leaflet

• 1. What Novidin is and what it is used for
• 2. Important information before taking Novidin
• 3. How to take Novidin
• 4. Possible side effects
• 5. How to store Novidin
• 6. Contents of the pack and other information

1. What Novidin is and what it is used for

Novidin contains 400 mg of hydroxychloroquine sulfate. Hydroxychloroquine is an antimalarial medicine belonging to the group of 4-hydroxychloroquines (combining rapid schizonticidal action in the blood and gametocytocidal activity), also classified as a slow-acting antirheumatic drug. Novidin is indicated for use in adults for:

• prevention and treatment of uncomplicated malaria caused by sensitive strains of Plasmodium, as an alternative to chloroquine (if first-line treatment is unsuitable or unavailable),
• symptomatic treatment of rheumatoid arthritis,
• treatment of systemic and discoid lupus erythematosus,
• treatment of skin diseases caused by sun exposure (photodermatoses).

Novidin is indicated for use in adolescents (from 12 years of age) and children from 6 to 11 years of age (ideal body weight ≥ 31 kg) for:

• treatment of systemic lupus erythematosus,
• treatment of discoid lupus erythematosus,
• prevention and treatment of uncomplicated malaria caused by sensitive strains of Plasmodium, as an alternative to chloroquine (if first-line treatment is unsuitable or unavailable),
• treatment of juvenile idiopathic arthritis (in combination with other treatment methods).

Hydroxychloroquine is not effective against chloroquine-resistant strains of P. falciparum and does not exhibit activity against the extraerythrocytic forms (hypnozoites) of P. vivax and P. ovale. Therefore, it does not prevent infection caused by these organisms when given prophylactically, nor does it prevent relapses of infection caused by these organisms.

2. Important information before taking Novidin

When not to take Novidin:

• if you are allergic to hydroxychloroquine or any of the other ingredients of this medicine (listed in section 6),
• if you have retinopathy or maculopathy,
• if you are allergic to 4-aminoquinoline compounds (antimalarial drugs).

Novidin should not be given to children under 6 years of age (ideal body weight <31 kg).< p>

Warnings and precautions

Before starting treatment with Novidin, you should discuss with your doctor or pharmacist in the following situations:

• liver or kidney disorders or if you are taking medicines that may affect the liver and/or kidneys (dose adjustment may be necessary),
• gastrointestinal disorders,
• nervous system disorders,
• blood diseases,
• metabolic disorders,
• heart conduction disorders,
• quinine hypersensitivity,
• deficiency of the enzyme called glucose-6-phosphate dehydrogenase (an enzyme found in red blood cells),
• porphyria (a hereditary metabolic disorder),
• inactive chronic infection with viral hepatitis B;
• epilepsy,
• concomitant use of potentially nephrotoxic or hepatotoxic drugs,
• previously diagnosed psoriasis,
• pregnancy or breastfeeding.

Hydroxychloroquine may cause low blood sugar levels. You should ask your doctor to inform you about the symptoms of low blood sugar levels. It may be necessary to check your blood sugar levels. During treatment with Novidin, you should protect yourself from direct sunlight. You should not take medicines containing gold salts or phenylbutazone (drugs used in rheumatoid arthritis and gout) at the same time. Before starting prolonged treatment with Novidin, it is recommended to have an eye examination (to check visual acuity and color vision, examine the central field of vision, and examine the fundus of the eye) and regular follow-up eye examinations, at least every 3 months, throughout the treatment period. These follow-up examinations should be tailored to the individual patient, in the following situations:

• in patients whose daily dose exceeds 6.5 mg/kg of ideal body weight (lean body weight, see section 3 "How to take Novidin");
• in patients with renal impairment;
• in patients whose cumulative dose exceeds 200 g;
• in elderly patients;
• in patients with decreased visual acuity.

You should stop taking Novidin if you experience any visual disturbances (e.g., decreased visual acuity or loss of color vision) and consult your doctor for a repeat eye examination. The risk of retinal disorders depends mainly on the dose. With daily doses less than 6.5 mg/kg of body weight, the risk is low. If this dose is exceeded, the risk of retinal disorders increases significantly. During long-term treatment, regular blood tests should also be performed, as well as muscle and tendon function tests. If abnormalities occur (e.g., changes in blood or muscle weakness), your doctor will decide whether to stop taking Novidin. In patients treated with hydroxychloroquine, cases of cardiomyopathy have been reported, some of which were fatal. Your doctor will monitor subjective and objective symptoms of cardiomyopathy. Treatment with Novidin should be discontinued if cardiomyopathy occurs. If a patient has been diagnosed with conduction disorders (bundle branch block, atrioventricular block) and biventricular hypertrophy, chronic toxicity may be suspected. Novidin may cause heart rhythm disturbances in some patients. You should exercise caution when taking Novidin if you have congenital QT interval prolongation (visible on an ECG, which is an electrical recording of heart activity) or if such prolongation occurs in your family, if you have acquired QT interval prolongation, if you have heart disorders or have had a heart attack in the past, if you have electrolyte imbalances in the blood (especially low potassium or magnesium levels, see "Novidin and other medicines"). If you experience palpitations or irregular heartbeat during treatment, you should immediately inform your doctor. You should follow the recommended dose, as the risk of heart disorders may increase with dose escalation. The treatment period should not exceed 3 years. Patients with a history of seizures should be regularly monitored by their doctor. Hydroxychloroquine has a cumulative effect, so it may take several weeks for therapeutic effects to appear in the treatment of rheumatoid arthritis or systemic lupus erythematosus. Therefore, side effects may occur very quickly. The effectiveness of treatment can be assessed after at least 4 to 12 weeks. If no improvement is observed after 6 months, treatment should be discontinued. In the case of malaria treatment, it should be considered that in countries with known chloroquine resistance, hydroxychloroquine should be used in combination with other medicines. During treatment with Novidin, movement disorders (extrapyramidal disorders) may occur. In some individuals treated with Novidin, mental health disorders may occur, such as irrational thoughts, anxiety, hallucinations, disorientation, or depression, including suicidal thoughts or behaviors, even in individuals who have not experienced such disorders before. If you or someone around you notices the occurrence of such side effects (see section 4), you should seek medical help immediately. Serious skin rashes have been reported with hydroxychloroquine (see section 4 "Possible side effects"). Often, the rash can involve ulceration of the mouth, throat, nose, genitals, and conjunctivitis (redness and swelling of the eyes). The occurrence of such serious skin rashes is often preceded by flu-like symptoms, such as fever, headache, and body aches. The rash can transform into widespread blisters and skin peeling. If such skin symptoms occur, you should stop taking hydroxychloroquine and immediately consult your doctor. Renal and hepatic impairment Patients with liver or kidney impairment, as well as those taking medicines that affect these organs, may need to have their dose reduced.

Children

Children are very sensitive to the group of medicines to which Novidin belongs. Therefore, you should exercise particular caution and store this medicine in a place that is out of sight and reach of children to avoid poisoning.

Elderly patients

There is no data on the comparison of hydroxychloroquine use in elderly patients versus other age groups.

Novidin and other medicines

You should tell your doctor or pharmacist about all medicines you are taking or have recently taken, as well as any medicines you plan to take. Some medicines may interact with hydroxychloroquine. It is essential to inform your doctor about taking the following medicines:

• So-called basic therapeutics (drugs used in the treatment of rheumatoid arthritis). These drugs, when used concomitantly with Novidin, may enhance side effects, so their concomitant use with hydroxychloroquine should be avoided.
• Digoxin (a drug used in heart failure). Concomitant administration with Novidin may increase the effect of digoxin. Your doctor should closely monitor the treatment.
• Antacids (drugs used to treat excessive stomach acid production) may reduce the absorption of Novidin. You should always maintain at least a 4-hour interval between taking Novidin and antacids.
• Cimetidine (an inhibitor of stomach acid production) may delay the elimination of Novidin.
• Neostigmine or pyridostigmine (drugs used to treat unwanted muscle relaxation). When used concomitantly with Novidin, the effect of neostigmine or pyridostigmine may be reduced.
• Aminoglycosides (drugs used to treat infections). Concomitant use with Novidin may enhance the inhibition of nerve-muscle conduction.
• Pyrimethamine/sulfadoxine (antimalarial drugs): concomitant use of Novidin with pyrimethamine/sulfadoxine significantly increases the risk of skin reactions.
• Insulin: Novidin may enhance the effect of diabetes medications (e.g., insulin), and dose reduction of insulin or other antidiabetic drugs may be necessary.
• You should inform your doctor if you are taking any medicines that affect heart rhythm. These include drugs used to treat heart rhythm disorders (antiarrhythmic drugs), depression (tricyclic antidepressants), mental disorders (antipsychotic drugs), bacterial infections, or malaria (e.g., halofantrine).
• Cyclosporine (a drug used after organ transplants). Concomitant use with Novidin may increase cyclosporine blood levels.
• Mefloquine, bupropion (drugs that lower the seizure threshold): hydroxychloroquine may lower the seizure threshold. Concomitant use with Novidin may increase the risk of seizures.
• Antiepileptic drugs: the effectiveness of some antiepileptic drugs may be reduced when used concomitantly with Novidin.
• Agalsidase (used to treat α-galactosidase deficiency). When used concomitantly with Novidin, the effect of agalsidase may be reduced.
• Praziquantel (an antiparasitic drug). When used concomitantly with Novidin, the blood level of praziquantel may decrease.
• Phenylbutazone (a pain reliever). When used concomitantly with Novidin, the risk of exfoliative dermatitis (a skin disorder with peeling skin) may increase.
• Hepatotoxic substances (you should avoid consuming large amounts of alcohol) and MAO inhibitors (drugs used to treat depression) should not be used with Novidin.
• Tamoxifen (a drug used to treat breast cancer). It is known that when used concomitantly with Novidin, it causes toxic effects on the retina.
• Probenecid (a drug that prevents increased uric acid levels) and indomethacin (an inhibitor of inflammatory processes): concomitant use with Novidin may increase the risk of hypersensitivity and retinopathy.
• Corticosteroid derivatives (drugs used to treat allergies and inflammatory conditions): concomitant use with Novidin may enhance myopathy (muscle disease) or cardiomyopathy (heart muscle disease).
• Folate antagonists, such as methotrexate (used to treat cancer): concomitant use with Novidin may enhance the effect of folate antagonists.
• Ampicillin (an antibiotic): concomitant use with Novidin may reduce ampicillin absorption.
• Chloroquine phosphate (an antimalarial drug): concomitant use with Novidin may lead to interactions, as this substance has a similar structure to hydroxychloroquine. Therefore, the following side effects cannot be excluded.
• Metronidazole (an antibiotic): acute dystonic reactions (changes in muscle tone and movement) have been observed after metronidazole administration.
• Penicillamine (an antirheumatic drug) may increase the risk of hematologic and/or renal side effects, as well as skin reactions.
• Vaccinations. The antibody response to the HDC vaccine against rabies may be reduced (intramuscular vaccination is recommended for rabies prophylaxis). The impact on routine vaccinations (tetanus, diphtheria, measles, polio, typhus, and tuberculosis) has not been monitored.
• Hydroxychloroquine inhibits the CYP2D6 enzyme. Therefore, CYP2D6 inhibitors should not be taken concomitantly with Novidin.

Novidin and alcohol

You should avoid consuming large amounts of alcohol.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, ask your doctor or pharmacist for advice before taking this medicine. Your doctor will discuss with you whether Novidin is suitable for you. Pregnancy During pregnancy, Novidin should not be used in high daily doses, unless your doctor considers it necessary, as the risk associated with stopping treatment is greater than the risk posed by the medicine to the fetus. A slight increase in the risk of serious birth defects may be associated with Novidin. Breastfeeding Hydroxychloroquine passes into breast milk. There is insufficient information on the effects of hydroxychloroquine in newborns and infants. Depending on the patient's condition and the duration of treatment, your doctor will decide whether to use this medicine during breastfeeding. If you are taking this medicine once a week, e.g., for malaria prophylaxis, it is not necessary to stop breastfeeding. However, this amount of medicine is not sufficient to prevent malaria in the infant. Rheumatoid arthritis, lupus: Due to the long half-life and high daily dose of hydroxychloroquine, a cumulative effect should be expected. Fertility There is no data on the effects of hydroxychloroquine on human fertility. In animal studies, chloroquine, a substance from which hydroxychloroquine is derived, reduced testosterone secretion, testicular and epididymal weight, and caused abnormal sperm formation.

Driving and using machines

You should not drive or operate machinery until you know how the medicine affects you. Side effects may occur, such as dizziness and visual disturbances. In some individuals, Novidin may cause side effects that affect the ability to drive or operate machinery. You should exercise caution, as hydroxychloroquine may cause decreased vision and blurred vision. These side effects may occur especially at the beginning of treatment. Using hydroxychloroquine in combination with alcohol or sedatives may affect the ability to drive or operate machinery.

3. How to take Novidin

Always take this medicine exactly as your doctor or pharmacist has told you. If you are not sure, ask your doctor or pharmacist. For oral use only. Take the tablet with food or a glass of milk. The tablet can be divided into equal doses. The dose should be adjusted according to body weight. In overweight individuals, the dose should be determined based on ideal body weight, not actual body weight. If dosing is based on actual body weight, overweight individuals may be at risk of overdose. Rheumatoid arthritisAdults:Initially, 400 to 600 mg per day. Maintenance dose: 200 to 400 mg per day. Juvenile idiopathic arthritisChildren and adolescents:The minimum effective dose should be used, which should not exceed 6.5 mg/kg of body weight per day based on ideal body weight or 400 mg per day (whichever is lower). Systemic and discoid lupus erythematosusAdults and adolescents:Initially, 400 to 600 mg per day. Maintenance dose: 200 to 400 mg per day. Maintenance dose: Body weight mg of hydroxychloroquine per day 31-49 kg 200 mg 50-64 kg 200 mg one day, 400 mg the next day, then 200 mg one day, etc. ≥ 65 kg 400 mg Children and adolescents:The minimum effective dose should be used, which should not exceed 6.5 mg/kg of body weight per day based on ideal body weight. PhotodermatosesAdults:400 mg per day, in a single dose. Treatment should be carried out only during periods of maximum sun exposure. Malaria prophylaxisThe medicine should be taken on the same day of the week, every week of therapy. In endemic areas of Plasmodium ovale and/or Plasmodium vivax, it is recommended to use prymachin phosphate prophylaxis in the last two weeks of therapy or immediately after completing hydroxychloroquine prophylaxis (see section 4.4). Adults:400 mg (1 tablet) once a week. Prophylaxis should start one week before arrival in the malaria-endemic area and continue for at least four weeks after leaving the area. Children and adolescents:Prophylaxis should start two weeks before arrival in the malaria-endemic area and continue for at least four weeks after leaving the area. Long-term use should be avoided in malaria prophylaxis in children. The weekly prophylactic dose is 6.5 mg/kg of body weight, but should not exceed the maximum adult dose, regardless of body weight. Treatment of uncomplicated malariaIn cases of documented Plasmodium ovale and/or Plasmodium vivax infections, prymachin phosphate should be added to the treatment for radical cure (see section 4.4). Adults:Initially, 800 mg (2 tablets), after 6 hours 400 mg (1 tablet), and then 400 mg (1 tablet) per day for the next 2 days or 3 days in individuals weighing over 60 kg. Children and adolescentsAdolescents (from 12 years of age) and children from 6 years of age (≥ 31 kg): During 2 days of treatment, the maximum therapeutic dose of 30 mg/kg of body weight should be administered, based on ideal body weight, as follows: Initially: 13 mg/kg of body weight (not exceeding 800 mg). Second dose: 6.5 mg/kg of body weight (not exceeding 400 mg), after 6 hours. Third dose: 6.5 mg/kg of body weight (not exceeding 400 mg), after 24 hours from the first dose. Fourth dose: 6.5 mg/kg of body weight (not exceeding 400 mg), after 48 hours from the first dose. Special patient groupsPatients with impaired renal or hepatic function During treatment of patients with impaired renal or hepatic function, dose adjustment may be necessary. Children and adolescentsThe minimum effective dose should be used, and the maximum adult dose should not be exceeded, regardless of body weight. Hydroxychloroquine is contraindicated in children under 6 years of age (ideal body weight <31 kg) (see section 2).< p>

Overdose of Novidin

If you have taken more than the prescribed dose of Novidin, you should immediatelyinform your doctor or go to the hospital emergency department. Overdose of 4-aminoquinolines is particularly dangerous in infants, as ingestion of only 1 to 2 grams of the substance has been fatal in them. Symptoms of overdose may include headaches, visual disturbances, cardiovascular collapse, seizures, and changes in rhythm and conduction, followed by sudden and early cessation of circulation and breathing. Given that these symptoms may occur after ingestion of a large dose, treatment must be immediate.

Missed dose of Novidin

You should not take a double dose to make up for a missed dose.

Stopping Novidin treatment

You should continue taking Novidin until your doctor tells you to stop. You should not stop taking Novidin if you feel better. Stopping treatment too early may cause the disease to progress.

4. Possible side effects

Like all medicines, Novidin can cause side effects, although not everybody gets them. Gastrointestinal side effects are the most common side effects, occurring in 10-20% of patients. Side effects may resolve on their own or after dose reduction and can usually be prevented by following the recommended monitoring. Usually, the observed side effects are reversible, but irreversible side effects have also been reported (e.g., deafness, changes in the visual field). In patients with psoriasis, there seems to be an increased risk of severe skin reactions. You should stop taking Novidin immediately and consult your doctor if you experience any of the following serious side effects — you may need urgent medical attention:

• Severe skin reactions (see section 2. Warnings and precautions), such as:
• rash with flu-like symptoms and fever, and swollen lymph nodes. This may be a condition called drug reaction with eosinophilia and systemic symptoms (DRESS).
• blisters, widespread skin peeling, pus-filled spots, occurring with fever. This may be a condition called acute generalized exanthematous pustulosis (AGEP).
• blisters or skin peeling around the lips, eyes, mouth, nose, and genitals, flu-like symptoms, and fever. This may be a condition called Stevens-Johnson syndrome (SJS).
• multiple skin lesions, itching, joint pain, fever, and general malaise. This may be a condition called toxic epidermal necrolysis (TEN).
• skin reactions, including (purple, raised, painful lesions, especially on the arms, hands, fingers, face, and neck), which may be accompanied by fever. This may be a condition called Sweet's syndrome.
• liver problems. Symptoms may include general malaise, with or without jaundice (yellowing of the skin and whites of the eyes), dark urine, nausea, vomiting, and/or abdominal pain. Rare cases of liver failure (including fatal cases) have been observed.

Very common side effects(may affect more than 1 in 10 people)

• Nausea
• Abdominal pain

Common side effects(may affect up to 1 in 10 people)

• Decreased appetite
• Emotional instability, such as irritability, nervousness, and agitation
• Headache
• Visual disturbances, such as seeing rings in the visual field, blurred vision, sensitivity to light, changes in visual acuity, and double vision
• Diarrhea with weight loss
• Bloating
• Vomiting
• Rash
• Itching (observed in approximately 40% of patients with lupus)
• Sensory disturbances

Uncommon side effects(may affect up to 1 in 100 people)

• Nervousness, insomnia or drowsiness, confusion or paresthesia
• Dizziness
• Changes in the retina causing vision impairment, changes in the visual field, irregular pigmentation of the retina, and retinal damage
• Tinnitus
• Abnormal liver function tests
• Causing or exacerbating liver function disorders
• Hair loss
• Changes in skin pigmentation and mucous membranes
• Depigmentation and hair loss

Rare side effects(may affect up to 1 in 1,000 people)

• Inhibition of new blood vessel formation (bone marrow)
• Blood changes, such as decreased white blood cell count (leukopenia and agranulocytosis), decreased platelet count (thrombocytopenia), and anemia (anemia and aplastic anemia)
• Heart diseases (cardiomyopathy)
• Swelling of the skin and/or mucous membranes
• Bullous rash
• Urticaria

Very rare side effects(may affect up to 1 in 10,000 people)

• Reversible phospholipidosis (increased intracellular accumulation of phospholipids)
• Liver function disorders

Frequency not known(cannot be estimated from the available data)

• Bronchospasm leading to shortness of breath
• Metabolic disorders (porphyria)
• Low blood sugar levels
• Feeling depressed (depression) or having suicidal thoughts or behaviors, hallucinations, feeling anxious or agitated, feeling disoriented, restlessness, sleep disturbances, feeling elated or overexcited.
• Seizures, convulsions, extrapyramidal disorders, such as muscle tone disorders, involuntary movements, inability to sit still, tremors
• Corneal clouding, corneal edema, restricted visual field, blurred vision, sensitivity to light
• Maculopathy and macular degeneration
• Hearing loss
• Affecting the liver and liver failure
• Exacerbation of psoriasis
• Muscle weakness or decreased muscle function (myopathy or neuromyopathy), which may be reversible after treatment discontinuation
• Decreased tendon reflexes
• Nerve conduction disorders
• Changes in heart rhythm (your doctor may check the electrical activity of your heart with an electrocardiogram)
• Reactions to light
• Exfoliative dermatitis (a skin disorder with peeling skin)
• Polymorphic erythema (fever, rash on the face, arms, and legs).

Reporting side effects

If you experience any side effects, including any not listed in this leaflet, you should inform your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Drug Monitoring, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, Tel.: +48 22 49 21 301, Fax: +48 22 49 21 309, Website: https://smz.ezdrowie.gov.pl. Side effects can also be reported to the marketing authorization holder. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Novidin

Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of that month. There are no special precautions for storage of the medicinal product. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Novidin contains

The active substance is hydroxychloroquine sulfate. Each film-coated tablet contains 400 mg of hydroxychloroquine sulfate (equivalent to 310 mg of hydroxychloroquine). The other ingredients are: Tablet core: Calcium hydrogen phosphate (E 341) Corn starch Povidone (E 1201) Magnesium stearate (E 572) Tablet coating (Opadry 85F18422 White) Polyvinyl alcohol (E 1203) Titanium dioxide (E 171) Macrogol (E 1521) Talc (E 553b)

What Novidin looks like and contents of the pack

White, oblong, biconvex tablets, 400 mg, with a break line. Length: approximately 14 mm Width: approximately 7 mm Height: approximately 6 mm Novidin film-coated tablets are packaged in PVC/Aluminum blisters, in a cardboard box. Pack size: 30 tablets.

Marketing authorization holder

Gebro Pharma GmbH Bahnhofbichl 13 6391 Fieberbrunn Austria

Manufacturer

Recipharm Parets, S.L.U C/ Ramón y Cajal, 2 08150 Parets del Vallès, Barcelona Spain

For further information on this medicine, please contact the local representative of the marketing authorization holder:

medac GmbH Sp. z o.o. Branch in Poland ul. Postępu 21 B 02-676 Warsaw tel. +48 22 430 00 30 fax +48 22 430 00 31 email: [email protected]

This medicine is authorized in the Member States of the European Economic Area under the following names:

Spain: Duplaxil Poland: Novidin

Date of last revision of the leaflet: 16.06.2023